SEPSECS

Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase

Basic information

Region (hg38): 4:25120013-25160550

Links

ENSG00000109618 ∙ NCBI:51091 ∙ OMIM:613009 ∙ HGNC:30605 ∙ Uniprot:Q9HD40 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia type 2D (Definitive), mode of inheritance: AR
• pontocerebellar hypoplasia type 2D (Moderate), mode of inheritance: AR
• pontocerebellar hypoplasia type 2D (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 2D (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 2 (Supportive), mode of inheritance: AR
• progressive cerebello-cerebral atrophy (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia, type 2D	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	12920088; 20920667; 25044680

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SEPSECS gene.

• not provided (43 variants)
• Pontocerebellar hypoplasia type 2D (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SEPSECS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	164		165
missense		4	75	2	2	83
nonsense	12	4	2			18
start loss	1	1				2
frameshift	31	4				35
inframe indel			1			1
splice donor/acceptor (+/-2bp)		11				11
splice region		4	3	35	5	47
non coding			42	114	26	182
Total	44	24	121	280	28

Highest pathogenic variant AF is 0.00000658

Variants in SEPSECS

This is a list of pathogenic ClinVar variants found in the SEPSECS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-25120061-T-A		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 12, 2018)
4-25120083-G-A		Pontocerebellar hypoplasia type 2D	Benign (Jan 12, 2018)
4-25120156-T-C		Pontocerebellar hypoplasia type 2D	Benign (Jan 12, 2018)
4-25120523-AATT-A		Pontoneocerebellar hypoplasia	Uncertain significance (Jun 14, 2016)
4-25120529-T-C		Pontocerebellar hypoplasia type 2D	Likely benign (Jan 12, 2018)
4-25120697-A-T		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 12, 2018)
4-25120797-G-T		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 13, 2018)
4-25120849-T-C		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 12, 2018)
4-25120941-C-G		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 12, 2018)
4-25120965-T-C		Pontocerebellar hypoplasia type 2D	Benign (Apr 27, 2017)
4-25121010-T-C		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 12, 2018)
4-25121015-T-C		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 13, 2018)
4-25121060-A-G		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 13, 2018)
4-25121091-A-G		Pontocerebellar hypoplasia type 2D	Benign (Jan 12, 2018)
4-25121223-C-T		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 12, 2018)
4-25121237-T-C		Pontocerebellar hypoplasia type 2D	Likely benign (Apr 27, 2017)
4-25121286-T-C		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 12, 2018)
4-25121313-G-T		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 12, 2018)
4-25121451-A-C		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 13, 2018)
4-25121631-T-C		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 12, 2018)
4-25121681-T-C		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 12, 2018)
4-25121722-T-C		Pontocerebellar hypoplasia type 2D	Likely benign (Apr 27, 2017)
4-25121752-A-G		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 13, 2018)
4-25121808-T-C		Pontocerebellar hypoplasia type 2D	Benign (Jan 12, 2018)
4-25122204-C-T		Pontocerebellar hypoplasia type 2D	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SEPSECS	protein_coding	protein_coding	ENST00000382103	11	40578

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.61e-8	0.846	125583	0	165	125748	0.000656

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0214	269	270	0.996	0.0000128	3260
Missense in Polyphen		94	105.42	0.89171		1293
Synonymous	2.10	69	95.0	0.726	0.00000455	972
Loss of Function	1.60	16	24.6	0.651	0.00000138	295

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000507	0.000507
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.0000544	0.0000544
Finnish	0.00537	0.00537
European (Non-Finnish)	0.000229	0.000229
Middle Eastern	0.0000544	0.0000544
South Asian	0.000164	0.000163
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Converts O-phosphoseryl-tRNA(Sec) to selenocysteinyl- tRNA(Sec) required for selenoprotein biosynthesis. {ECO:0000269|PubMed:17142313}.
• Pathway: Selenocompound metabolism - Homo sapiens (human);Aminoacyl-tRNA biosynthesis - Homo sapiens (human);Selenium Metabolism and Selenoproteins;Selenocysteine synthesis;Metabolism of amino acids and derivatives;selenocysteine biosynthesis;Metabolism;Selenoamino acid metabolism (Consensus)

Recessive Scores

• pRec: 0.156

Intolerance Scores

• loftool: 0.412
• rvis_EVS: 0
• rvis_percentile_EVS: 53.73

Haploinsufficiency Scores

• pHI: 0.223
• hipred: N
• hipred_score: 0.353
• ghis: 0.579

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.209

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sepsecs

Gene ontology

• Biological process: selenocysteine incorporation;selenocysteine metabolic process;selenocysteinyl-tRNA(Sec) biosynthetic process
• Cellular component: nucleus;cytoplasm;cytosol
• Molecular function: tRNA binding;protein binding;phosphoseryl-selenocysteinyl-tRNA selenium transferase activity